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Reference Genomes Advance Human Microbiome Studies

Researchers have published an analysis of 178 genomes from microbes
that live in or on the human body. The accomplishment sets the
stage to better understand how these diverse organisms affect human
health and disease.

Entercoccus faecalis, a microbe that lives
in the human gut. Image courtesy of US Department of Agriculture.

The microorganisms living in and on the human body outnumber the
body’s cells by 10 to 1. Some of these bacteria, fungi and
viruses cause illnesses, but many are necessary for good health.
Currently, researchers can grow only some in the laboratory. But
using new genomic techniques, scientists can identify minute amounts
of microbial DNA and compare sequences in databases.

The Human Microbiome Project (HMP) was launched by NIH in 2008
to catalog and explore the diverse microbial species—or microbiome—that
inhabit the human body. Part of the first phase includes sequencing
hundreds of microbial reference genomes. The effort is funded through
the NIH Common Fund and involves several NIH components. Sequencing
work for the project is done by HMP-funded large-scale sequencing
centers around the country. Samples for the first phase are being
collected from 5 body areas: the digestive tract, mouth, skin,
nose and vagina.

The researchers described the 178 microbial genomes that launch
the HMP reference collection in the May 21, 2010, issue of Science.
The scientists found almost 30,000 previously undiscovered, unique
proteins. Among them were proteins produced by bacteria that live
in the stomach that may contribute to gastric ulceration, a hole
in the stomach lining. The scientists also found novel proteins
associated with the metabolism of sugars and amino acids.

The analysis demonstrates that genomes sequenced as part of the
reference collection will add directly to our understanding of
the human microbiome. However, the researchers note that the microbiome
is much more complex than the set of genomes thus far in the reference
collection. The first stage of the project focused on bacteria,
but the HMP reference collection is eventually expected to total
about 900 genomes, including those of fungi and viruses.

"Although this is only the first step in making HMP medically
useful, we already have learned surprising things about the diversity
and complexity of the microorganisms that live in and on our body," says
Dr. Jane Peterson, a leader of the HMP effort at NIH’s National
Human Genome Research Institute (NHGRI). "The next stages
of this coordinated study will begin to associate the presence
or absence of specific micro-organisms with various states of health
and illness."

The HMP is currently funding pilot demonstration projects to sample
the microbiomes of volunteers who are healthy or who have specific
diseases. This will allow researchers to study changes in the microbiome
at particular body sites in healthy controls compared to patients
affected by diseases. These studies will use samples collected
from 7 areas of the body: the digestive tract, the mouth, the skin,
the nose, the vagina, the blood and the male urethra.